Oncotarget

Research Papers:

Deguelin inhibits non-small cell lung cancer via down-regulating Hexokinases II-mediated glycolysis

Wei Li, Feng Gao, Xiaoqian Ma, Ruike Wang, Xin Dong and Wei Wang _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:32586-32599. https://doi.org/10.18632/oncotarget.15937

Metrics: PDF 2185 views  |   HTML 2942 views  |   ?  


Abstract

Wei Li1,2,*, Feng Gao3,4,*, Xiaoqian Ma1,2,*, Ruike Wang5,*, Xin Dong6, Wei Wang1,2

1Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410000, P.R. China

2Cell Transplantation and Gene Therapy Institute, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, 410000, P.R. China

3Powder Metallurgy Research Institute of Central South University, Changsha, Hunan, 41000, P.R. China

4Department of Ultrasonography, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan, 410000, P.R. China

5Xiangya School of Medicine, Central South University, Changsha, Hunan, 410000, P.R.China

6State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100000, P.R. China

*These authors contributed equally to this work

Correspondence to:

Wei Wang, email: weiw_bio@163.com

Keywords: non-small cell lung cancer, deguelin, Hexokinases II, Akt, glycolysis

Received: October 10, 2016     Accepted: February 22, 2017     Published: March 06, 2017

ABSTRACT

Hexokinases II (HK2) is a hub in the regulation of cancer cell glycolysis. Here we reported deguelin, a natural compound which has been studied in various tumor types, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via directly down-regulating of glycolysis. In NSCLC cell lines and primary NSCLC tissue, we found HK2 is overexpressed. Deguelin treatment markedly inhibited anchorage-dependent and independent growth of NSCLC cell lines. We revealed that deguelin exposure impaired glucose metabolism by inhibiting Akt-mediated Hexokinase II expression, overexpression of constitutively activated Akt1 substantially rescued deguelin-induced glycolysis suppression. Moreover, deguelin suppressed HK2 presence on mitochondrial outer membrane and induced apoptosis. The in vivo data indicated that deguelin prominently restrained tumor development in a xenograft mouse model. Thus, deguelin appears to be a promising new therapeutic agent for lung cancer and may be considered for further studies in other animal models and in clinical trials.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 15937